Pathogenesis of cytomegalovirus infection after organ transplantation

巨细胞病毒（CMV）相关性肺炎（CMV- p）是器官移植受者的主要并发症，尽管其发病机制尚不清楚。这项研究就是为了解决这个问题而组织起来的。1998-1999年，获得了以下结果：（C3HxBALB/c） F1小鼠于4周前接种0.2 LD50的小鼠巨细胞病毒（MCMV），注射亲代脾细胞诱导GVH。随后，MCMV- dna以一氧化氮（NO）依赖的方式在肺和心脏中检测到，提示NO在MCMV再激活中起作用。然而，这些涌现的DNA并没有被转移到RNA上。因此，潜在MCMV.2的完全重新激活可能需要其他因素。在成年BALB/c小鼠或（C57BL/6xSv129） F1小鼠中腹腔注射0.2 LD50（50%致死剂量）的（MCMV） 4周后，在无病毒的肺中单次注射抗cd3单抗可诱发CMV-P。在免疫组织化学中，在细支气管上皮细胞中检测到硝基酪氨酸，表明这些细胞是CMV-P模型的靶向细胞。相比之下，CMV-P不能在诱导型一氧化氮氧化酶合成酶敲除（iNOS KO）小鼠中被诱导。在体外实验中，来自mcmv感染小鼠的T细胞（其中仅在唾液腺中检测到病毒）在抗cd3刺激下显示不为诱导终止信号。这可能就是为什么mcmv感染的小鼠在体内抗cd3刺激时产生的细胞因子比未感染的对照小鼠高的原因。

Cytomegalovirus (CMV)-associated pneumonitis (CMV-P) is a major complication in organ transplant recipients, although its pathogenesis has been still unclear. This research was organized to solve this problem. In 1998-1999, the following results were obtained.1. (C3HxBALB/c) F1 mice, which had been inoculated with 0.2 LD50 of murine cytomegalovirus (MCMV) at 4 wk before, were injected with parental spleen cells to induce GVH. Thereafter, MCMV-DNA could be detectable in the lungs and hearts in Nitric Oxice (NO)-dependent manner, suggesting that NO played a role in MCMV reactivation. However, such emergent DNA was not transferred to RNA. Thus, other factor(s) may be required for the full reactivation of latent MCMV.2. Four weeks after intraperitoneal inoculating of 0.2 LD50 (50% lethal dose) of (MCMV) in adult BALB/c mice or in (C57BL/6xSv129) F1 mice, CMV-P was evoked by a single injection of anti-CD3 mAb in the lungs free of the virus. In immunohistochemistry, nitrotyrosine was detected in the bronchioepithelial cells, suggesting that the cells were targeted in our model of CMV-P. In contrast, CMV-P could not be induced in inducible Nitric Oxidase Synthetase knock-out (iNOS KO) mice.3. In in vitro assay, T cells from MCMV-infected mice, in which the virus was detected only in the salivary glands, were revealed not to be induced termination signals upon anti-CD3 stimulation. This may be the why MCMV-infected mice produced higher amounts of cytokines upon anti-CD3 stimulation in vivo, than those of uninfected control mice.